bims-hemali Biomed News
on Hematologic malignancies
Issue of 2025–11–23
forty papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό
  1. Nilotinib versus imatinib with early switch from imatinib to nilotinib to obtain treatment-free remission in newly diagnosed chronic myeloid leukemia patients: the analysis of the first co-primary endpoint.
  2. Big cells, bigger BTK resistance in mantle cell lymphoma.
  3. Isatuximab: surface strike, deep response in AL amyloidosis.
  4. One lipid to predict them all.
  5. Ropeginterferon alfa-2b in Polycythemia Vera: redefining disease control through molecular targeting.
  6. A comparative study of hematologic response to ropeginterferon alfa-2b in hydroxyurea-resistant or intolerant polycythemia vera: a real-world data-based analysis.
  7. Isatuximab for relapsed AL amyloidosis.
  8. iMMune profiling comes of age.
  9. Real-World Comparative Effectiveness of Bruton Tyrosine Kinase Inhibitors in Relapsed/Refractory Mantle Cell Lymphoma.
  10. Integrative profiling strategies to guide personalized therapy in mantle cell lymphoma: a pilot study.
  11. Emerging first-line treatment approaches for mantle cell lymphoma.
  12. HLA diversity is associated with TKI response and treatment-free remission in chronic myeloid leukemia.
  13. Orelabrutinib plus reduced-dose whole brain radiotherapy in elderly primary central nervous system lymphoma: a case report.
  14. Dreaming of a Better Future: Drug Development in Myeloma.
  15. Experience of Using a Bruton Tyrosine Kinase (BTK) Inhibitor in Primary Testicular Diffuse Large B-Cell Lymphoma (DLBCL) with Isolated Central Nervous System (CNS) Metastasis.
  16. Hemoglobin changes during long-lasting frontline treatment with Tyrosine-Kinase inhibitors in patients with chronic myeloid leukemia.
  17. Clonal identification and homology differentiate primary central nervous system lymphoma from non-central nervous system lymphoplasmacytic lymphoma: a case report.
  18. Decitabine plus all-trans retinoic acid versus decitabine monotherapy for myelodysplastic syndromes with excess blasts: a multicenter, randomized controlled trial.
  19. Sustained remission in relapsed/refractory diffuse large B cell lymphoma following Glofitamab discontinuation due to JC virus reactivation: balancing efficacy and infectious risk.
  20. Brentuximab vedotin combined with cisplatin, cytarabine, and dexamethasone treatment in transplant-eligible Korean patients with relapsed or refractory Hodgkin's lymphoma.
  21. Early Positron Emission Tomography Response-Adapted Treatment in Low-Risk Diffuse Large B-Cell lymphoma: an open label, multicenter, randomised, non-inferiority phase 3 trial.
  22. Confirmation by conformation: rescue of mutant p53 in AML.
  23. Limitations of rituximab in treating primary immune thrombocytopenia and the therapeutic potentials of alternatives.
  24. Iron Deficiency Anemia: Evaluation and Management.
  25. Bispecific antibody therapy in CNS myeloma: Early evidence from a multicentre cohort.
  26. Transformation and survival in patients with Waldenström macroglobulinemia: a population-based study.
  27. Radiotherapy dose-response of mycosis fungoides with large cell transformation.
  28. Effect of tyrosine kinase inhibitors on sperm parameter and pituitary gonadal axis in males with chronic myeloid leukemia: a prospective cohort study.
  29. Mechanisms and interventions in relapsed/refractory extranodal natural killer/T-cell lymphoma.
  30. Old problems, new tools: ZR2 in older patients with DLBCL.
  31. Relapsed or refractory central nervous system lymphoma successfully treated by glofitamab combined with lenalidomide.
  32. JAK inhibitor selection in challenging scenarios of myelofibrosis: a review.
  33. A pooled primate screen finds that MYD88-CD40 boosts CAR-T.
  34. Catalytic Inhibition of p300 Preferentially Targets IRF4 Oncogenic Activity and Tumor Growth in Multiple Myeloma.
  35. Prognosis and Treatment of Plasmablastic Lymphoma in the United States: A Multicenter Retrospective Study.
  36. The SCARLET Trial: Radiotheranostics in Multiple Myeloma.
  37. PSP-0119: Targeted IRAK4 Degradation as a Novel Therapeutic Strategy for FLT3-Mutant AML.
  38. Efficacy and safety of inotuzumab ozogamicin and its combination therapies in acute lymphoblastic leukemia: a systematic review and meta-analysis.
  39. A matching-adjusted indirect comparison of survival outcomes with pirtobrutinib (BRUIN) versus standard of care (SCHOLAR-2) in relapsed/refractory mantle cell lymphoma previously treated with a covalent Bruton tyrosine kinase inhibitor.
  40. Rapid loss of viability in acute myeloid leukemia cells upon telomerase inactivation.
  1. Leukemia. 2025 Nov 18.
    Nilotinib versus imatinib with early switch from imatinib to nilotinib to obtain treatment-free remission in newly diagnosed chronic myeloid leukemia patients: the analysis of the first co-primary endpoint.
    Fausto Castagnetti, Massimo Breccia, Elisabetta Abruzzese, Renato Bassan, Gianni Binotto, Massimiliano Bonifacio, Giovanni Caocci, Isabella Capodanno, Francesco Cavazzini, Giuseppe Cimino, Paola Fazi, Antonella Gozzini, Alessandra Iurlo, Jeroen J W M Janssen, Monia Lunghi, Roberto Marasca, Bruno Martino, Monica Messina, Francesco Muriano, Francesca Paoloni, Alfonso Piciocchi, Gianantonio Rosti, Antonella Russo Rossi, Giuseppe Saglio, Simona Sica, Simona Soverini, Agostino Tafuri, Daniele Vallisa, Peter E Westerweel, Fabrizio Pane.
      Treatment-free remission is one of the most important goals of CML treatment but so far, the best treatment to reach this aim is still undefined, even though it is widely accepted that a sustained DMR is the prerequisite to discontinue TKI. Here we report on the depth of the molecular response, the first co-primary end point of the SUSTRENIM study, in a cohort of newly diagnosed CP-CML patients randomized 1:1 to be treated with nilotinib or with imatinib followed by switching to nilotinib in absence of optimal response. Of the 448 enrolled patients, 228 and 220 were randomized to the nilotinib (NIL) and imatinib (IM) arms, respectively, and followed for a median of 45.9 months. Eighty-two (37.2%) of the 220 patients on the IMarm did not fulfill the ELN criteria for optimal response of treatment and switched to nilotinib therapy. At the 24 months of follow-up, 107 of the 448 patients reached an MR4.5 response with a significantly higher frequency within the patients on the nilotinib arm (65 vs 42; p = 0.02). The analysis of the first primary endpoint indicates that, despite the early switch in the IM-randomized patients, NIL therapy is more effective to induce DMR.
    DOI:  https://doi.org/10.1038/s41375-025-02796-z
  2. Blood. 2025 Nov 20. 146(21): 2500-2501
    Big cells, bigger BTK resistance in mantle cell lymphoma.
    Justin Taylor.
      
    DOI:  https://doi.org/10.1182/blood.2025029937
  3. Blood. 2025 Nov 20. 146(21): 2495-2496
    Isatuximab: surface strike, deep response in AL amyloidosis.
    Eli Muchtar, Angela Dispenzieri.
      
    DOI:  https://doi.org/10.1182/blood.2025031062
  4. Blood. 2025 Nov 20. 146(21): 2504-2505
    One lipid to predict them all.
    Kevin Rouault-Pierre.
      
    DOI:  https://doi.org/10.1182/blood.2025031007
  5. Expert Rev Anticancer Ther. 2025 Nov 19.
    Ropeginterferon alfa-2b in Polycythemia Vera: redefining disease control through molecular targeting.
    Laura De Fazio, Matteo Molica, Marco Rossi.
       INTRODUCTION: This review critically appraises recent clinical and translational advances on ropeginterferon alfa-2b, a long-acting, mono-pegylated interferon that has become a key therapeutic option for polycythemia vera (PV). Beyond its cytoreductive efficacy, ropeginterferon exerts immunomodulatory and antiproliferative effects that may modify disease biology. The review outlines its therapeutic rationale, pharmacologic profile, and emerging role as a disease-modifying agent compared with conventional cytoreductive therapies.
    AREAS COVERED: This article summarizes the pharmacokinetic properties, clinical efficacy, molecular activity, and safety of ropeginterferon alfa-2b across pivotal trials and real-world studies. Particular attention is given to hematologic responses, reduction of JAK2 V617F allele burden, and long-term tolerability. Data were identified through a systematic search of PubMed, Embase, and ClinicalTrials.gov for English-language studies published up to 2025.
    EXPERT OPINION: Ropeginterferon alfa-2b has redefined PV management by combining durable hematologic control with progressive molecular remission. Its favorable efficacy-toxicity balance and convenient dosing support long-term use, particularly in younger or treatment-naïve patients. Future research should refine patient selection, explore predictive biomarkers, and define its role among disease-modifying agents capable of transforming PV into a chronic, potentially controllable disorder.
    Keywords:  Cytoreduction; JAK2 V617F; Polycythemia Vera; disease modification; hematologic response; molecular remission; ropeginterferon alfa-2b
    DOI:  https://doi.org/10.1080/14737140.2025.2592736
  6. Blood Res. 2025 Nov 17. 60(1): 61
    A comparative study of hematologic response to ropeginterferon alfa-2b in hydroxyurea-resistant or intolerant polycythemia vera: a real-world data-based analysis.
    Sung-Eun Lee, Seug Yun Yoon, Sung-Yong Kim, Soo-Mee Bang, Insoo Lee, Jihyuk Lee, Junshik Hong.
       PURPOSE: To compare the hematologic response to ropeginterferon alfa-2b versus available therapies in patients with hydroxyurea-resistant or intolerant polycythemia vera (HU-R/I PV) using propensity-matched real-world data.
    METHODS: This retrospective propensity-matched cohort study compared a single-arm clinical trial cohort with a historical control cohort from five Korean institutions. We included 36 HU-R/I patients from a prospective phase II trial (PV IIT, registration number KCT0006138) and 81 matched historical controls. Propensity score matching and weighted analyses balanced the baseline characteristics (age, sex, disease duration, hematologic parameters, and HU status). The primary endpoint was a complete hematologic response (CHR) at 48 weeks.
    RESULTS: At 48 weeks, ropeginterferon alfa-2b achieved significantly higher CHR rates (52%; 95% confidence interval [CI]: 35-70%) than historical controls (15%; 95% CI: 8-27%; odds ratio 0.15; 95% CI: 0.07-0.33; p < 0.0001). This superiority remained consistent across various matching ratios and weighted analyses. Subgroup analyses showed higher response rates to ropeginterferon alfa-2b, regardless of HU status (resistant vs. intolerant), age (< 60 vs. ≥ 60 years), or disease duration (< 5 vs. ≥ 5 years). In the control group, the most common regimen was a combination of HU and phlebotomy (53%) with limited use of ruxolitinib (5.5%). Analyses confirmed robustness with no significant baseline imbalances after matching.
    CONCLUSION: Ropeginterferon alfa-2b demonstrated superior early hematologic efficacy compared with conventional salvage therapies in Korean patients with HU-R/I PV. Extended follow-up is warranted to assess the long-term clinical benefits.
    Keywords:  Hydroxyurea; Polycythemia vera; Real-world evidence; Ropeginterferon alfa-2b
    DOI:  https://doi.org/10.1007/s44313-025-00110-5
  7. Blood. 2025 Nov 20. 146(21): 2615
    Isatuximab for relapsed AL amyloidosis.
      
    DOI:  https://doi.org/10.1182/blood.2025031732
  8. Blood. 2025 Nov 20. 146(21): 2496-2498
    iMMune profiling comes of age.
    Bruno Paiva, Aintzane Zabaleta.
      
    DOI:  https://doi.org/10.1182/blood.2025030836
  9. Blood Adv. 2025 Nov 21. pii: bloodadvances.2025017160. [Epub ahead of print]
    Real-World Comparative Effectiveness of Bruton Tyrosine Kinase Inhibitors in Relapsed/Refractory Mantle Cell Lymphoma.
    Tycel J Phillips, Mengyang Di, Taavy Miller, Jingru Wang, Amy Pierre, Gregory A Maglinte, Erlene K Seymour, Yucai Wang.
      This real-world retrospective cohort study evaluated utilization and comparative effectiveness of covalent Bruton tyrosine kinase inhibitor (cBTKi) monotherapies in relapsed/refractory mantle cell lymphoma (R/R MCL) from electronic health records in the United States. Adults with R/R MCL who received second- or third-line (2L/3L) zanubrutinib, acalabrutinib, or ibrutinib monotherapy, on or after January 1, 2018, were included. Inverse probability of treatment weighting was used in adjusted Cox models to compare real-world time-to-next treatment (rwTTNT) and overall survival (rwOS). Among 698 patients who received 2L/3L cBTKi monotherapy, 49%, 32%, and 19% received acalabrutinib, ibrutinib, and zanubrutinib, respectively. Unadjusted analyses showed median rwTTNT for 2L zanubrutinib, acalabrutinib, and ibrutinib was 14.5 (95%CI 11.0-23.2), 12.8 (95%CI 10.5-15.6), and 10.3 (95%CI 7.6-13.7) months and median rwOS was 26.4 (95%CI 23.2-not reached [NR]), 29.2 (95%CI 22.9-38.1), and 29.3 (95%CI 21.8-41.6) months, respectively. Median rwTTNT for 3L zanubrutinib, acalabrutinib, and ibrutinib was 21.1 (95%CI 3.9-NR), 9.2 (95%CI 6.8-14.7), and 9.6 (95%CI 4.8-18.0) months and median rwOS was NR (95%CI 27.3-NR), 27.4 (95%CI 15.1-42.2), and 27.0 (95%CI 15.6-NR) months, respectively. Adjusted models in the 2L/3L cohorts combined showed numerically longer rwTTNT and statistically significantly longer rwOS for zanubrutinib versus ibrutinib (hazard ratio 0.63, 95%CI 0.42-0.96), and trends for improved rwTTNT and rwOS for zanubrutinib over acalabrutinib. Toxicity was a frequent reason for changing to another cBTKi. These findings suggest potential improvements in rwTTNT and rwOS with the use of second- and next-generation cBTKis for R/R MCL from 2018 and beyond.
    DOI:  https://doi.org/10.1182/bloodadvances.2025017160
  10. NPJ Precis Oncol. 2025 Nov 21. 9(1): 373
    Integrative profiling strategies to guide personalized therapy in mantle cell lymphoma: a pilot study.
    Yang Liu, Holly A Hill, Yijing Li, Joseph McIntosh, Vivian Jiang, Fangfang Yan, Yixin Yao, Yue Fei, Jared Zhang, Lawrence Qu, Jun Yao, Preetesh Jain, Ken Chen, Michael Wang.
      Mantle cell lymphoma (MCL) responds to frontline therapy but is susceptible to relapse. While Bruton's tyrosine kinase inhibitors (BTKi) achieve high response rates, most patients eventually experience disease progression. Predicting responses to subsequent treatments remains challenging due to the lack of an established platform. Heterogeneity in gene alterations and cellular pathways contribute to resistance, complicating treatment approaches. Here, we present a multi-modal profiling platform, targeting key pathways rather than focusing on singular DNA-associated lesions. We identified dysregulated signaling pathways by performing gene expression profiling on 20 MCL samples using a custom MCL MATCH gene set and analyzed the data with gene-set variation analysis. We also screened 22 therapeutics in vitro to assess their efficacy. Whole exome sequencing was conducted to identify prevalent and actionable mutations linked to enriched pathways. Finally, we tested selected therapeutics in patient-derived xenograft mouse models to predict potential response in corresponding patients. Based on our integrative profiling, we identified the top therapeutic candidates for three patients in this study. This integrative platform may help identify targeted therapies for BTKi-relapsed/refractory MCL patients in clinical settings.
    DOI:  https://doi.org/10.1038/s41698-025-01158-3
  11. Leuk Lymphoma. 2025 Nov 17. 1-11
    Emerging first-line treatment approaches for mantle cell lymphoma.
    Changchun Deng, Nikki Agarwal, Ariel D Sindel.
      Treatment of mantle cell lymphoma (MCL) is evolving rapidly. In the front-line setting important recent developments include (1) approval of the BTK inhibitor (BTKi) acalabrutinib in combination with the chemoimmunotherapy, (2) evidence that the BTKi ibrutinib given with induction chemotherapies and during maintenance phase is highly effective, (3) BTKi without chemotherapy has produced promising results, (4) BCL2 inhibitor venetoclax and BTKi can be combined to effectively treat high risk MCL with TP53 alterations, and (5) consolidation with autologous stem cell transplant (ASCT) may not provide additional efficacy benefit for patients who have received highly effective first-line treatments but may be associated with substantial toxicities. These results support a concerted effort to bring BTKi to the first-line treatment of MCL. This review focuses on key clinical trials that provide the above insights and provides a succinct review of relevant historical regimens to guide oncologists in the management of untreated MCL.
    Keywords:  Neoplasia; chemotherapeutic approaches; lymphoma and Hodgkin disease; pharmacotherapeutics
    DOI:  https://doi.org/10.1080/10428194.2025.2586079
  12. Hemasphere. 2025 Nov;9(11): e70261
    HLA diversity is associated with TKI response and treatment-free remission in chronic myeloid leukemia.
    Charles Toulemonde, Valérie Dubois, Christophe Bouvier, Alexandre Ridao, Marie-Claire Archier, Marie Balsat, Sophie Ducastelle, Fiorenza Barraco, Gaelle Fossard, Julie Hildt, Julien Bollard, Mauricette Michallet, Hélène Labussière-Wallet, Sandrine Hayette, Franck-Emmanuel Nicolini, Vincent Alcazer.
      Immune surveillance is increasingly recognized as a key determinant of cancer treatment outcomes. However, the impact of Human Leukocyte Antigen (HLA) diversity in chronic myeloid leukemia (CML) remains poorly understood and has been scarcely investigated. We retrospectively analyzed 367 CML patients with high-resolution HLA typing to investigate the impact of HLA allele distribution and HLA evolutionary divergence (HED) on disease susceptibility, molecular response, and treatment-free remission (TFR). Compared to 2832 healthy donors, CML patients exhibited significantly lower HED scores for all class I loci (A, B, C) and HLA-DQB1 (FDR < 0.001), suggesting a narrower immunopeptidome repertoire at diagnosis. Specific alleles, such as HLA-A*30:01 (OR [95% CI] = 2.08 [1.26-3.25]) and B*14:02 (OR = 1.90 [1.26-2.79]), were associated with increased CML risk (FDR < 0.01). Among 289 patients with clinical follow-up, HLA-DQB1*06:04 (aHR [95% CI] = 3.71 [1.57-8.77]) and DRB1*13:02 (aHR = 3.95 [1.77-8.81]) were associated with faster MR4 achievement in imatinib-treated patients (FDR < 0.01), while B*44:02 (aHR = 4.83 [1.62-14.41]) predicted favorable response to dasatinib (FDR < 0.05). In the TFR cohort (n = 105), alleles A*26:01 (aHR = 3.47 [1.44-8.38]), A32:01 (aHR = 3.28 [1.52-7.09], FDR < 0.05), and B18:01 (aHR = 12.96 [3.59-46.77], FDR < 0.001) were significantly associated with increased relapse risk. Conversely, a higher HED score for HLA-C was associated with improved TFR in dasatinib-treated patients (P = 0.0067). These findings suggest that HLA genotype and class-specific HED may influence CML susceptibility and outcomes and could inform TKI selection and discontinuation strategies.
    DOI:  https://doi.org/10.1002/hem3.70261
  13. Front Oncol. 2025 ;15 1693481
    Orelabrutinib plus reduced-dose whole brain radiotherapy in elderly primary central nervous system lymphoma: a case report.
    Qiao Wang, Hua Wang, Duozhuang Tang, Yuanyuan Wu, Siyao He, Si Tao.
       Background: Primary central nervous system lymphoma (PCNSL) primarily affects elderly individuals, many of whom are unable to tolerate standard high-dose methotrexate (HD-MTX) chemotherapy due to frailty and comorbid conditions. There is a pressing need for alternative treatment strategies that offer reduced toxicity while maintaining therapeutic efficacy.
    Case presentation: In this case report, we describe three elderly patients (aged 70-78 years) with newly diagnosed, chemotherapy-ineligible PCNSL who were treated with a combination of reduced-dose whole brain radiotherapy (rd-WBRT, <30 Gy) and oral orelabrutinib (150 mg daily).
    Conclusion: These preliminary findings suggest that the all patients initially achieved either complete remission (CR) or partial remission (PR). Two patients maintained durable remission, whereas one patient experienced disease relapse after discontinuing orelabrutinib and switching to an alternative regimen. No significant neurotoxicity or treatment-related complications were observed. Combination of orelabrutinib and rd-WBRT may represent a safe and effective therapeutic approach for elderly patients with PCNSL who are not candidates for standard chemotherapy. Prospective clinical trials are warranted to further evaluate this approach.
    Keywords:  BTKi; PCNSL; chemotherapy-ineligible; elderly patients; neurotoxicity; rd-WBRT
    DOI:  https://doi.org/10.3389/fonc.2025.1693481
  14. Blood Adv. 2025 Nov 21. pii: bloodadvances.2024015740. [Epub ahead of print]
    Dreaming of a Better Future: Drug Development in Myeloma.
    Sagar Lonial, Richa Parikh.
      
    DOI:  https://doi.org/10.1182/bloodadvances.2024015740
  15. J Clin Pract Res. 2025 May;47(3): 328-331
    Experience of Using a Bruton Tyrosine Kinase (BTK) Inhibitor in Primary Testicular Diffuse Large B-Cell Lymphoma (DLBCL) with Isolated Central Nervous System (CNS) Metastasis.
    Santhosh Meedimale, Soumya Surath Panda, Adya Kinkar Panda, Debahuti Mohapatra, Rajesh Kumar Bhola, Lalatendu Moharana, Swati Sucharita Mohanty, Lipsita Samantaray.
       Background: Primary testicular lymphoma (PTL) is a rare subtype of non-Hodgkin's lymphoma (NHL), most commonly presenting as diffuse large B-cell lymphoma (DLBCL). It primarily affects older men and has a tendency to relapse in the central nervous system (CNS), contralateral testis, and lungs. Although rituximab has improved survival outcomes, its limited CNS penetration is a clinical challenge.
    Case Report: We report the case of a 39-year-old man diagnosed with primary testicular DLBCL (PT-DLBCL) (triple expresser). He received six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin (hydroxydaunorubicin), vincristine (oncovin), and prednisone) combined with high-dose methotrexate (HD-MTX) and contralateral testicular radiation. After 33 months of disease-free survival, he experienced a CNS relapse. He was subsequently treated with the MAR (methotrexate, cytarabine, and rituximab) regimen, consisting of HD-MTX, cytarabine (Ara-C), and rituximab. Following whole-brain radiotherapy and rituximab maintenance therapy, he achieved complete response and was transitioned to maintenance therapy with acalabrutinib.
    Conclusion: This case highlights the successful use of the MAR regimen and acalabrutinib maintenance in a patient with CNS-relapse PT-DLBCL. Further studies are needed to develop standardized treatment protocols for such high-risk cases.
    Keywords:  BTK inhibitor; CNS prophylaxis; DLBCL; acalabrutinib; extranodal sites
    DOI:  https://doi.org/10.14744/cpr.2025.96241
  16. Leuk Lymphoma. 2025 Nov 17. 1-6
    Hemoglobin changes during long-lasting frontline treatment with Tyrosine-Kinase inhibitors in patients with chronic myeloid leukemia.
    Roberto Latagliata, Ida Carmosino, Ambra Di Veroli, Emilia Scalzulli, Claudia Ielo, Gioia De Angelis, Roberta Laureana, Cinzia De Gregoris, Maria Laura Bisegna, Giulio Trapè, Maurizio Martelli, Massimo Breccia.
      To assess the impact of imatinib compared to 2 G-TKIs on hemoglobin (Hb) in the long-lasting frontline treatment, 242 patients with chronic myeloid leukemia (CML) from 2 Centers still receiving frontline TKI after 5 years [186 (76.8%) imatinib and 56 (23.2%) 2 G-TKIs] were evaluated. Baseline rate of patients with mild/moderate anemia (Hb < 11 g/dl) was lower in those treated with imatinib (18.2% vs 35.7% with 2 G-TKIs, p = 0.006), while at the 60th month became significantly higher in those treated with imatinib (15.6% vs 3.6% with 2 G-TKI, p = 0.018). Event-free and Overall Survival beyond the 60th month in patients receiving imatinib with anemia at that time-point were significantly shorter than in patients without anemia (p < 0.001 and p = 0.002, respectively). Long-lasting treatment with imatinib caused late anemia in about 15% of patients at the 60th month. This event, which seems very rare with 2 G-TKIs, affected survival and should be recognized in the long-term management of CML patients.
    Keywords:  2g-TKI; Chronic myeloid leukemia; imatinib; late anemia
    DOI:  https://doi.org/10.1080/10428194.2025.2586816
  17. J Med Case Rep. 2025 Nov 21. 19(1): 605
    Clonal identification and homology differentiate primary central nervous system lymphoma from non-central nervous system lymphoplasmacytic lymphoma: a case report.
    Yuko Tanaka, Nahoko Furuya, Seiichi Okabe, Seiichiro Yosizawa, Seiichiro Katagiri, Michiyo Asano, Tamiko Suguro, Mitsuru Moriyama, Akiko Yamada, Shunsuke Ohtsuki, Hiroaki Fujimoto, Daigo Akahane, Moritaka Gotoh, Maki Tanigawa, Jun Matubayashi, Shinjiro Fukami, Michihiro Kohno, Toshitaka Nagao, Naoya Nakamura, Akihiko Gotoh.
       BACKGROUND: Lymphoplasmacytic lymphoma/Waldenström macroglobulinemia rarely transforms into diffuse large B-cell lymphoma, and there have been no reports of cases proving clonal identity when presenting as primary central nervous system lymphoma. There are many unclear aspects regarding the mechanism by which lymphoplasmacytic lymphoma/Waldenström macroglobulinemia infiltrates the central nervous system and transforms, as well as the treatment methods for the transformed lymphoma.
    CASE PRESENTATION: A 49-year-old Asian Japanese male was emergently transported due to loss of consciousness, revealing a tumorous lesion in the brain. He was diagnosed with primary central nervous system lymphoma following an endoscopic biopsy and treated with immunochemotherapy included high-dose methotrexate. During the second course of immunochemotherapy, a computed tomography scan conducted to investigate bilateral lower leg edema revealed tumorous lesions in both lower legs. A biopsy of the thigh node specimen was diagnosed as lymphoplasmacytic lymphoma. When high-dose methotrexate including immunochemotherapies was finished, the lymphoma lesions in central nervous system had disappeared. However, the symptoms of bilateral lower leg edema were prominent because of remaining the bilateral thigh nodes, so additional immunochemotherapy for lymphoplasmacytic lymphoma/Waldenström macroglobulinemia was administered, resulting in complete remission of the lymphoplasmacytic lymphoma/Waldenström macroglobulinemia as well. primary central nervous system lymphoma, and he has maintained both lymphomas for 4 years. The myeloid differentiation factor 88 (MYD88) gene mutation was detected in primary central nervous system lymphoma and lymphoplasmacytic lymphoma/Waldenström macroglobulinemia lymphoma cells. The same clonal origin of primary central nervous system lymphoma and lymphoplasmacytic lymphoma/Waldenström macroglobulinemia was confirmed according to homology in a region of the immunoglobulin heavy chain V (IGHV) gene. On the basis of the characteristics of primary central nervous system lymphoma and lymphoplasmacytic lymphoma/Waldenström macroglobulinemia, we speculated that the lymphoplasmacytic lymphoma/Waldenström macroglobulinemia lymphoma cells had already invaded the central nervous system, a condition called Bing-Neel syndrome, and transformed into primary central nervous system lymphoma cells after a certain period.
    CONCLUSION: It was revealed that the lymphoma cells of both lymphoplasmacytic lymphoma/Waldenström macroglobulinemia and primary central nervous system lymphoma derived from a common cell possessing MYD88. The utility of adding chemotherapy for low-grade lymphoma in addition to therapy for primary central nervous system lymphoma is not clear. While lymphoplasmacytic lymphoma is a low-grade lymphoma that does not always require chemotherapy, combining treatment for lymphoplasmacytic lymphoma and primary central nervous system lymphoma may contribute to the effectiveness of both treatments.
    Keywords:  Homology of IGHV ; Lymphoplasmacytic lymphoma; Primary central nervous system lymphoma; Waldenström macroglobulinemia
    DOI:  https://doi.org/10.1186/s13256-025-05677-2
  18. Haematologica. 2025 Nov 20.
    Decitabine plus all-trans retinoic acid versus decitabine monotherapy for myelodysplastic syndromes with excess blasts: a multicenter, randomized controlled trial.
    Xinping Zhou, Yanjuan Lin, Yan Gao, Zheng Ge, Li Huang, Jin Zhang, Hai Cheng, Guifang Ouyang, Fanjun Meng, Yulu Tian, Yuemin Kuang, Fengping Zhou, Lixia Sheng, Weimei Jin, Gaixiang Xu, Liya Ma, Li Ye, Chen Mei, Jian Li, Jie Jin, Hongyan Tong.
      Despite standard treatment with hypomethylating agents, the prognosis of patients with higher-risk myelodysplastic syndrome (MDS) remains poor. All-trans retinoic acid (ATRA) has demonstrated promising efficacy in unfit patients with acute myeloid leukemia. This multicenter controlled trial randomized (1:1) untreated patients with MDS with excess blasts (MDS-EB) to ATRA plus decitabine (ATRA at 25 mg/m2/day in 2 divided daily doses throughout the 28-day cycle plus decitabine at 20 mg/m2 on days 1-5) or decitabine alone (20 mg/m2 on days 1-5). The primary endpoint was the overall response rate within 4 treatment cycles. A total of 227 patients were randomized. Four patients who did not commence therapy were excluded from the modified intention-to-treat (mITT) analysis. The median patient age was 62 years (range: 19-81). The overall response rate was 78% (86/110) in the ATRA group versus 51% (58/113) in the decitabine group (odds ratio [OR] 3.40; 95% confidence interval [CI] 1.90-6.09; p.
    DOI:  https://doi.org/10.3324/haematol.2025.288526
  19. Curr Res Transl Med. 2025 Nov 06. pii: S2452-3186(25)00058-3. [Epub ahead of print]74(1): 103549
    Sustained remission in relapsed/refractory diffuse large B cell lymphoma following Glofitamab discontinuation due to JC virus reactivation: balancing efficacy and infectious risk.
    Massimiliano Marinoni, Lucrezia De Marchi, Federico Meconi, Alice Di Rocco, Luca Franceschini, Marco Iannetta, Manuela Rizzo, Massimiliano Postorino, Adriano Venditti, Fabiana Esposito.
       BACKGROUND: The therapeutic landscape for relapsed/refractory diffuse large b-cell lymphoma (R/R DLBCL) is expanding, with bispecific antibodies emerging as key treatment strategies. These drugs have demonstrated high efficacy in this setting of patient, but leading to prolonged immunosuppression, exposing patients to a high risk of infections. We describe a R/R DLBCL patient achieving complete remission (CR) with glofitamab, although discontinued due to JC virus reactivation. Nineteen months post-treatment, the patient remains in CR, with declining viral copies and no evidence of neurological complications. The patient also has a history of chronic myeloid leukemia (CML), currently in treatment free remission (TFR). This is an example of durable DLBCL remission despite abbreviated glofitamab therapy, while highlighting challenges in balancing immunotherapy efficacy with opportunistic infection risks.
    Keywords:  Bispecific antibodies; Diffuse large B cell lymphoma; JC virus
    DOI:  https://doi.org/10.1016/j.retram.2025.103549
  20. Blood Res. 2025 Nov 21. 60(1): 62
    Brentuximab vedotin combined with cisplatin, cytarabine, and dexamethasone treatment in transplant-eligible Korean patients with relapsed or refractory Hodgkin's lymphoma.
    Jun Ho Yi, Young Hoon Park, Myung-Won Lee, Kwai Han Yoo, Junshik Hong, Hyeon-Seok Eom.
       PURPOSE: Brentuximab vedotin (BV)-based combinations have shown promising results in patients with relapsed or refractory Hodgkin's lymphoma (RRHL) in Western countries. We conducted a phase II study to further define the role of BV-based salvage therapy in transplant-eligible patients with RRHL in Korea.
    METHODS: Transplant-eligible patients with RRHL were recruited to receive two cycles of BV (1.8 mg/kg) plus DHAP (cisplatin 100 mg/m2, cytarabine 2 g/m2, and dexamethasone 40 mg). Autologous stem cells were collected from non-progressive patients who received one more cycle of BV-DHAP. After three cycles, the responding patients underwent autologous stem cell transplantation (ASCT). The primary endpoint was a complete metabolic response (CMR) rate after two cycles of BV-DHAP.
    RESULTS: Between April 2022 and August 2024, seven lymphoma cases were recruited. Owing to slow accrual, the study was terminated early. Their median age was 30 years (range, 24-62 years). All patients received at least two cycles of BV-DHAP; the overall response rate (ORR) was 100%, and four patients showed CMR (57%). One patient withdrew consent after the second cycle, and the other six patients received one more cycle of BV-DHAP, resulting in five patients achieving CMR (71%). One patient failed to receive ASCT, and all five patients who received ASCT achieved post-transplant CMR with a 80% complete response (CR) over a 12-month duration. Thrombocytopenia was the most common grade 3 or higher grade hematologic adverse events (n = 5). Grade 2 nausea occurred in three patients. Three patients experienced dose reduction, and four patients experienced treatment delays.
    CONCLUSIONS: Despite its encouraging early efficacy, the administration of BV-DHAP in Korean patients with RRHL requires careful monitoring due to toxicity concerns.
    Keywords:  Autologous stem cell transplantation; Brentuximab vedotin; Hodgkin's lymphoma
    DOI:  https://doi.org/10.1007/s44313-025-00097-z
  21. Ann Oncol. 2025 Nov 17. pii: S0923-7534(25)06264-7. [Epub ahead of print]
    Early Positron Emission Tomography Response-Adapted Treatment in Low-Risk Diffuse Large B-Cell lymphoma: an open label, multicenter, randomised, non-inferiority phase 3 trial.
    Jean-Marie Michot, Serge Bologna, Jean-Noël Bastie, Thierry Vander Borght, Josette Brière, Vincent Ribrag, Come Bommier, Frédéric Peyrade, Laure Lebras, Gandhi Damaj, Diane Coso, David Sibon, Christophe Bonnet, Franck Morschhauser, Hervé Ghesquières, Christophe Fruchart, Carole Soussain, Stéphanie Becker, Pierre Olivier, Anne Julian, Thierry Molina, Corinne Haioun, Hervé Tilly.
       BACKGROUND: Preliminary reports suggest interim positron emission tomography (PET) could drive treatment duration in limited-stage diffuse large B-cell lymphoma (DLBCL). This phase 3 randomised study in front-line therapy for DLBCL patients with adjusted-age IPI (aaIPI) risk = 0, evaluates an experimental PET-response adapted approach using PET response after 2 cycles of R-CHOP to de-escalate treatment duration.
    METHODS: LNH2009-1B study is a two-arms, open-label, multicenter, prospective, randomised phase 3 non-inferiority trial, evaluating treatment de-escalation based on PET after 2 cycles of R-CHOP in previously untreated DLBCL patients aged 18-80, with aaIPI =0. In the experimental PET-adapted arm, patients with negative PET after 2 cycles received in total 4 cycles of R-CHOP, whereas those with positive PET after 2 cycles received in total 6 cycles. In the standard arm, treatment was 6 cycles regardless of PET results after 2 cycles. No radiotherapy was planned. The primary endpoint was 3 years progression-free survival (PFS). The primary analysis was performed in the intention-to-treat population. The trial is registered with ClinicalTrial.gov, NCT01285765, recruitment is completed.
    RESULTS: 650 patients were enrolled, of whom 319 randomly assigned to PET-adapted arm and 331 in standard arm. In the PET-adapted arm, 77.7% of patients had PET negative after 2 cycles and received in total 4 cycles or R-CHOP. The 3-year PFS in PET-adapted and standard arm were 92.0% (95% CI 88.3-94.5) and 89.2% (95% CI 85.3-92.2), respectively (p-value =0.070). The non-inferiority of the experimental PET-adapted arm was demonstrated (hazard ratio 0.72, 95% CI: 0.47-1.12, p-value <0.0001). Patients in PET-adapted arm had fewer adverse events grades ≥ 3 (54.7% vs. 62.7%, p=0.046) and serious adverse events (9.5% vs. 14.2%, p=0.039).
    CONCLUSION: A risk-adapted approach using early PET after 2 cycles of R-CHOP was beneficial minimizing toxicity without compromising efficacy in patients treated in front-line therapy for low-risk DLBCL.
    DOI:  https://doi.org/10.1016/j.annonc.2025.11.006
  22. Blood. 2025 Nov 20. 146(21): 2503-2504
    Confirmation by conformation: rescue of mutant p53 in AML.
    David P Lane.
      
    DOI:  https://doi.org/10.1182/blood.2025030273
  23. Curr Opin Hematol. 2025 Nov 10.
    Limitations of rituximab in treating primary immune thrombocytopenia and the therapeutic potentials of alternatives.
    Lingxiao Pan, Jianfeng Zhu.
       PURPOSE OF REVIEW: Primary immune thrombocytopenia (ITP), an immune-mediated hemorrhagic disease, features an intricate pathogenesis that involves megakaryocyte malfunction and hyperresponsiveness of the innate and adaptive immune systems. As a second-line drug for ITP, rituximab acts quickly and can produce an initial response rate of up to 60%. However, this response only lasts for a short term, meanwhile challenged by resistance, relapse and side effects. Additionally, no reliable clinical parameters have been proposed for forecasting the therapeutic response of patients. Furthermore, the application of rituximab is restricted in specific populations, including pregnant patients, children with positive antithyroid antibodies, and patients contaminated with HBV.
    RECENT FINDINGS: Splenectomy and new drugs that target the thrombopoietin receptor, FcγR, FcRn, B-cells or plasma cells, T-cells, and complement pathways may overcome these shortcomings.
    SUMMARY: This article summarizes the barriers limiting the use of rituximab, and discusses the effectiveness and safety of current and fledgling treatment options.
    Keywords:  Immune thrombocytopenia; drug resistance; novel therapies; rituximab; special populations
    DOI:  https://doi.org/10.1097/MOH.0000000000000902
  24. Am Fam Physician. 2025 Nov;112(5): 538-545
    Iron Deficiency Anemia: Evaluation and Management.
    Kelly Latimer, Genta Baci, Michael Layne.
      Iron deficiency anemia is common worldwide. In adult patients without inflammation, a ferritin level of less than 45 ng/mL or ferritin level of 46 to 99 ng/mL plus a transferrin saturation of less than 20% is diagnostic of iron deficiency. In patients with inflammation, a ferritin level of less than 100 ng/mL is diagnostic. Risk factors for iron deficiency anemia include low socioeconomic status, female sex, age younger than 5 years, and chronic inflammation. Underlying causes should be investigated. Recurrent blood loss is responsible for 94% of cases. In younger patients with a plausible cause of iron deficiency anemia (eg, heavy menstrual bleeding), a reasonable approach is to treat the bleeding and provide iron supplementation. In men and postmenopausal women, bidirectional endoscopy should be performed. Noninvasive testing for Helicobacter pylori infection and celiac disease is recommended because both are common causes of iron deficiency anemia. Oral iron replacement is the first-line treatment for most patients. However, intravenous iron is recommended in patients with heart failure to increase exercise capacity. Every-other-day dosing of oral iron improves absorption. Approximately 50% of patients have decreased adherence due to adverse effects. Patients taking oral iron therapy should be evaluated for response in 2 to 4 weeks. Patients who cannot tolerate oral iron or do not have adequate response should receive intravenous iron. Hypersensitivity to newer formulations of intravenous iron is rare (less than 1%).
  25. Br J Haematol. 2025 Nov;207(5): 2161-2166
    Bispecific antibody therapy in CNS myeloma: Early evidence from a multicentre cohort.
    Alexandra Noveihed, Samer Al Hadidi, Meera Mohan, Mansi R Shah.
      
    Keywords:  CNS myeloma; bispecific antibodies; multiple myeloma; myelomatous meningitis; talquetamab; teclistamab
    DOI:  https://doi.org/10.1111/bjh.70108
  26. Discov Oncol. 2025 Nov 21. 16(1): 2137
    Transformation and survival in patients with Waldenström macroglobulinemia: a population-based study.
    Yu Du, Xiaona Chang, Xiangxiang Li, Shugang Xing.
       BACKGROUND: Waldenström's macroglobulinemia (WM) is a rare hematologic neoplasm characterized by an indolent clinical course. However, a significant proportion of patients undergo histological transformation to aggressive diffuse large B-cell lymphoma (DLBCL). Long-term population-based data on the transformation and survival are scarce. Based on the Surveillance, Epidemiology, and End Results (SEER) database, we performed this study to estimate the risk of transformation and outcomes of patients with WM.
    METHODS: 8191 patients with WM were retrieved from the SEER database. Competing risk methods were employed to evaluate the cumulative incidences and putative risk factors for transformation. Survival outcomes were analyzed using Kaplan-Meier and Cox proportional hazards regression.
    RESULTS: The cumulative incidence rates for transformation at 5 and 10 years were 1.0% (95% CI, 0.8%-1.3%) and 1.9% (95% CI, 1.5%-2.2%), respectively. A substantial increase in total mortality was related to the time-dependent transformation (HR, 4.21 [95% CI, 3.36-5.26]; P < 0.001). Patients who presented with transformation > 24 months after WM diagnosis had a longer overall survival (OS) than those who experienced transformation within 24 months (5-year rate, 81.9% [95% CI, 74.7%-89.9%] v 42.7% [95% CI, 26.4%-69.2%]; P < 0.001). The OS was shorter for patients with DLBCL transformed from WM than for those with matched de novo DLBCL (5-year rate, 28.0% [95% CI, 20.5%-38.1%] v 49.5% [95% CI, 41.2%-59.4%]; P = 0.001).
    CONCLUSIONS: Histological transformation to DLBCL was associated with significantly increased mortality in patients with WM, and the survival outcomes substantially worse than matched de novo DLBCL cases.
    Keywords:  Cumulative incidence; Risk factors; Survival outcome; Transformation; Waldenström macroglobulinemia
    DOI:  https://doi.org/10.1007/s12672-025-03946-6
  27. Radiother Oncol. 2025 Nov 19. pii: S0167-8140(25)05296-X. [Epub ahead of print] 111292
    Radiotherapy dose-response of mycosis fungoides with large cell transformation.
    Martin Higgins, Philippa Johnstone, H Miles Prince, Stephen Lade, Michael T Fahey, Chris McCormack, Carrie van der Weyden, Friyana Bhabha, Odette Buelens, Belinda A Campbell.
       BACKGROUND: Mycosis fungoides (MF) is the most prevalent subtype of primary cutaneous T-cell lymphoma. Large cell transformation of MF (LCTMF) is rare and confers a poor prognosis. Radiotherapy (RT) is an effective local treatment for LCTMF; however, dose-response data are limited.
    METHODS: Eligibility for this retrospective study required biopsy-proven LCTMF with clinico-pathological correlation, diagnosed 1/1/1990-1/10/2021, and managed at Peter MacCallum Cancer Centre.
    RESULTS: 83 patients were eligible. Median age was 68 years, 63 (76 %) patients had cutaneous-only LCTMF at time of diagnosis. Median follow-up was 8.0 (95 %CI: 6-11) years. Details of 155 irradiated LCTMF lesions (from 49 patients) were available: 150 cutaneous, 5 extra-cutaneous. For cutaneous LCTMF, median equivalent dose in 2.0 Gy-fractions (EQD2, α/β of 10) was 30.6 (range, 4.7-46.3) Gy. Dose-response data were available for 141 cutaneous LCTMF lesions. Overall response rate (ORR) was 94 % (59 % complete response (CR), 35 % partial response). For cutaneous lesions treated with >12.0 Gy, ORR was 100 %. Increasing doses of RT were associated with greater CR rates: doses >36.0 Gy achieved 100 % CR rate. 22 (27 %) patients with unifocal cutaneous-only LCTMF were treated with local RT-alone, median EQD2 36.0 Gy (range, 17.3-46.3 Gy). CR rate was 100 %. 9 (41 %) patients remained relapse-free (median follow-up, 3.2 years). Only 1 patient experienced infield-only recurrence at first relapse.
    CONCLUSION: LCTMF is radio-responsive, with EQD2 >12.0 Gy associated with 100 % ORR. Dose-response was observed, with EQD2 >36.0 Gy achieving 100 % CR rate. For unifocal cutaneous LCTMF, RT-alone achieved excellent infield control with possible curative potential in a proportion of patients.
    Keywords:  Cutaneous T-cell lymphoma; Large-cell transformation; Local control; Mycosis fungoides; Radiotherapy
    DOI:  https://doi.org/10.1016/j.radonc.2025.111292
  28. Leuk Lymphoma. 2025 Nov 20. 1-8
    Effect of tyrosine kinase inhibitors on sperm parameter and pituitary gonadal axis in males with chronic myeloid leukemia: a prospective cohort study.
    Neha Ganju, Mona Sharma, Rishi Dhawan, Gurleen Oberoi, Mukul Aggarwal, Pradeep Chaturvedi, Manoranjan Mahapatra, Tulika Seth.
      As the survival of patients with Chronic Myeloid Leukemia (CML) on tyrosine kinase inhibitors (TKIs) is comparable to healthy counterparts, it is now being treated as a chronic disease. Hence, there is significant concern of the effect of TKI on fertility and pregnancy outcomes. While the teratogenic effects of TKIs are well established, data on their impact on male fertility remain limited. With a growing number of CML patients of reproductive age being diagnosed annually, understanding the effect of Imatinib on male fertility is crucial. To study the effect of Imatinib (TKI) on the Pituitary gonadal axis and sperm parameters in CML patients, as there is limited data in this area. A prospective cohort study (Oct 2018-Jan 2021) included 30 male CML-CP patients (18-60 years). Patients were excluded if they had known dysfunction of the pituitary-gonadal axis, structural abnormalities of the gonads, or a history of prior sterilizing treatments. After receiving imatinib treatment for 3 months, out of these 30 patients, sperm concentration declined in 22 (73.3%), though only 5 (22.7%) had oligospermia (<15 million/ml), and none had severe oligospermia (<5 million/ml). Among these 5 patients, 4 were aged ≤35 years, while 1 was older than 35 years. Progressive motility decreased in 11 patients, with 6 (54.5%) dropping below the reference range (<32%), potentially causing infertility. Vitality decreased in 13 patients. Out of these, in 10 patients, vitality dropped below the reference range (<58%). Normal sperm morphology declined in 16 patients, but in only 2 patients it fell below 4%. Post-Imatinib treatment, two patients had elevated FSH, while LH and testosterone levels remained normal in all. Although there was a mild decrease in mean values of post-imatinib samples, there was no statistically significant decrease in mean FSH (p-value = 0.106), LH (p-value = 0.080), or testosterone levels (p = 0.313). Mean sperm concentration reduced after imatinib treatment, though it was not significant (p-value = 0.080). Mean progressive motility increased, but the change was not significant (p = 0.059). Mean sperm vitality increased, but it was not significant (p-value = 0.264). Also, there was no significant correlation found between hormonal changes and sperm parameters. Imatinib therapy was associated with a decline in sperm concentration, progressive motility, vitality, and normal morphology in some patients; however, no statistically significant changes were observed in mean hormonal or semen parameters. Patients planning families should nonetheless be counselled regarding the potential impact of TKIs on sperm quality. While sperm cryopreservation is not routinely recommended, its role in selected patients warrants evaluation in larger and long-term studies.
    Keywords:  CML; TKIs; pituitary gonadal axis; sperm; tyrosine kinase inhibitors
    DOI:  https://doi.org/10.1080/10428194.2025.2584688
  29. Drug Discov Today. 2025 Nov 18. pii: S1359-6446(25)00262-4. [Epub ahead of print] 104549
    Mechanisms and interventions in relapsed/refractory extranodal natural killer/T-cell lymphoma.
    Qisi Lu, Tao You, Qian Cheng, Zhe-Sheng Chen, Haiwen Huang.
      Extranodal natural killer/T-cell lymphoma (ENKTL) is an aggressive non-Hodgkin's lymphoma associated with Epstein-Barr virus and typically involves extranodal sites. The traditional CHOP regimen is no longer standard owing to drug resistance, whereas asparaginase-based therapies have become the mainstay of treatment. However, resistance and tumor invasion lead to relapses in 40-50% of patients, with 20% progressing to relapsed/refractory ENKTL, resulting in a median survival of <12 months. Management of ENKTL remains challenging, with an unmet clinical need. However, although the prognosis for relapsed/refractory ENKTL is poor, the development of new treatment strategies is progressing with a better understanding of the disease. This review examines factors contributing to treatment resistance, underlying resistance mechanisms and potential strategies to overcome ENKTL resistance.
    Keywords:  Extranodal natural killer/T-cell lymphoma; novel therapy; relapsed/refractory; targeted therapy; tumor drug resistance
    DOI:  https://doi.org/10.1016/j.drudis.2025.104549
  30. Blood. 2025 Nov 20. 146(21): 2501-2502
    Old problems, new tools: ZR2 in older patients with DLBCL.
    A Vera de Jonge, Martine E D Chamuleau.
      
    DOI:  https://doi.org/10.1182/blood.2025030855
  31. Front Oncol. 2025 ;15 1685271
    Relapsed or refractory central nervous system lymphoma successfully treated by glofitamab combined with lenalidomide.
    Yin-Yin Peng, Xiao-Qiong Tang.
       Background: Central nervous system lymphoma (CNSL) is rare and aggressive, which has high rates of recurrence and fatality. At present, there does not exist any standard treatment for the relapsed/refractory (R/R) CNSL.
    Methods: We retrospectively analyzed 4 patients with R/R CNSL, who were treated with gloftamab combined with lenalidomide between October 2024 and June 2025 at the First Affiliated Hospital of Chongqing Medical University. Treatment response was assessed by brain magnetic resonance imaging and cerebrospinal fluid cytology every two cycles.
    Results: The 4 R/R CNSL patients include 1 male and 3 females, with the mean age of 58 years (range: 51~69 years). Their clinical manifestations at relapse included headache, stupor, listlessness, lethargy, nausea, poor appetite, weak limbs, walking disorder, slurred speech and visual impairment. The mean relapse time was 5 months (range 3~8 months) after the last treatment. After 2 cycles of treatment, all patients achieved rapid remission (2 in CRu and 2 in PR), the overall response rate was 100% (4/4). They got deep remission after 4 cycles (3 in CR/CRu, 1 in PR). No patient experienced cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome nor hematological toxicity of grade 3 or above. Neither liver nor kidney dysfunction was observed. No treatment discontinuation occurred due to adverse events.
    Conclusions: The glofitamab-lenalidomide combination showed promising activity and excellent tolerability in R/R CNSL, potentially addressing the critical need for effective salvage regimens.
    Keywords:  central nervous system lymphoma; diffuse large B-cell lymphoma; primary; refractory; relapsed; secondary
    DOI:  https://doi.org/10.3389/fonc.2025.1685271
  32. Haematologica. 2025 Nov 20.
    JAK inhibitor selection in challenging scenarios of myelofibrosis: a review.
    Pankit Vachhani, Ruben Mesa, John Mascarenhas, Raajit Rampal, Stephen T Oh, Alessandro Maria Vannucchi, Maria Laura Fox, Francesca Palandri, Francesco Passamonti, Jean-Jacques Kiladjian, Mahshid Azimi, Claire Harrison, Prithviraj Bose.
      Myelofibrosis is a progressive myeloproliferative neoplasm characterized by dysregulated Janus kinase (JAK)/signal transducer and activator of transcription signaling. Common clinical manifestations include constitutional symptoms, splenomegaly, and anemia, which can significantly impact quality of life and survival. Although hematopoietic stem cell transplant is the only curative treatment modality in myelofibrosis, JAK inhibitors have transformed management by providing symptom relief and reducing spleen size in many patients; newer JAK inhibitors also offer anemia-related benefits. A total of four JAK inhibitors-ruxolitinib, fedratinib, pacritinib, and momelotinib-are now available for the treatment of myelofibrosis, each with distinct profiles and safety considerations that may inform selection. However, head-to-head trial comparisons are limited, and real-world experience with most of these JAK inhibitors is only just emerging; therefore, first-line selection and optimal sequencing in particular patients can be challenging. This review summarizes the current data surrounding available JAK inhibitors for the treatment of patients with myelofibrosis and examines how individual patient characteristics can help guide selection among them. To illustrate the diverse clinical factors and key considerations associated with JAK inhibitor selection in practice, we discuss these data in the context of four hypothetical patient cases representing possible real-world scenarios, offering treatment recommendations based on our collective expertise in the field. As the myelofibrosis therapeutic landscape continues to evolve, a thorough understanding of the strengths and limitations of each JAK inhibitor relative to a given patient's presentation will support individualized treatment decisions for optimal long-term outcomes.
    DOI:  https://doi.org/10.3324/haematol.2025.288654
  33. Blood. 2025 Nov 20. 146(21): 2498-2499
    A pooled primate screen finds that MYD88-CD40 boosts CAR-T.
    Mark B Leick.
      
    DOI:  https://doi.org/10.1182/blood.2025030745
  34. Cancer Res. 2025 Nov 17.
    Catalytic Inhibition of p300 Preferentially Targets IRF4 Oncogenic Activity and Tumor Growth in Multiple Myeloma.
    W Frank Lenoir, Michael R McKeown, Giulia Giorgetti, Marek J Kobylarz, Tamara D Hopkins, Wayne L Glore, Michelle G Shum, Yaretzi Calderón, Jessica Encinas Mayoral, Luis A Carvajal, Kameron R Mori, Jun Li, Hua Gao, Yupeng Zheng, Zhihua Ma, Nikolaus D Obholzer, Minyun Zhou, Benjamin W Trotter, Christopher J Dinsmore, Nikhil C Munshi, Charles Y Lin, Mariateresa Fulciniti, Peter B Rahl.
      The oncogenic transcription factor (TF) IRF4 is a currently undrugged universal multiple myeloma (MM) dependency. Using transcriptional regulatory network (TRN) mapping, an unbiased multi-omic target ID approach, we identified the coactivator lysine acetyltransferase (KAT) p300 as a key IRF4 partner. Validation of this preferential relationship through quantitative interactome mapping revealed that IRF4 was the most abundant MM specific dependency and more closely complexed with p300 than other TFs, such as IKZF1/IKZF3. Development of optimized p300 lysine acetyltransferase (KAT) inhibitors enabled inhibition of IRF4 activity and MM proliferation ex vivo and in vivo. p300/CBP KAT inhibition preferentially targeted MM cells over normal cells, specifically modulating the MM transcriptome, and the p300 KAT inhibitors more completely inhibited IRF4 activity at lower levels compared to existing p300/CBP bromodomain inhibitors. Furthermore, combining p300/CBP KAT inhibition and therapeutics with orthogonal mechanisms targeting transcription in MM elicited synergistic anti-tumor effects. Together, these data motivate the ongoing clinical development of p300/CBP KAT inhibition in MM.
    DOI:  https://doi.org/10.1158/0008-5472.CAN-25-3440
  35. Res Sq. 2025 Sep 30. pii: rs.3.rs-7607922. [Epub ahead of print]
    Prognosis and Treatment of Plasmablastic Lymphoma in the United States: A Multicenter Retrospective Study.
    Matthew Hamby, Brian Egleston, Zachary Frosch, Ralphael Steiner, Ariela Noy, Veronica Carvajal, Emeline Chong, Seda Tolu, Gaston Jean-Louis, Jennifer Amengual, Romil Patel, Sairah Ahmed, John Sharp, Timothy Voorhees, Robert Baiocchi, Andres Ramirez-Gamero, Jorge Castillo, Emily Hamburger, Christopher Dittus, Imran Nizamuddin, Neha Mehta-Shah, Nyein Nyein Thaw Dar, Jose Sandoval-Sus, Alexandra Rojek, Peter Riedell, Niloufer Khan, Alexey Danilov, Vinod Solipuram, Paul Rubinstein, Anthony Ariotti, Gita Suneja, Alexander Vartanov, Charles Milrod, Adam Olszewski, Gordon Smilnak, Emily Ayers, Sahaj Desai, Joanna Rhodes, Gabriella Magarelli, Tatyana Feldman, Meredith Pellon, David Aboulafia, William Bae, Carlos Galvez, Vineel Bhatlapenumarthi, Mehdi Hamadani, Stefan Barta.
      Plasmablastic lymphoma (PBL) is a rare, aggressive AIDS-related lymphoma observed in patients with immunosuppressed states as well as in immunocompetent individuals. We sought to determine survival outcomes, prognostic factors, and optimal treatment regimens in a large, contemporary cohort of patients with PBL in the United States. We performed a multicenter, retrospective cohort study, including 344 patients diagnosed with PBL between 2005 and 2022. Patients were stratified into cohorts according to underlying immune status. Survival outcomes were calculated using Kaplan-Meier statistics, with cohort-specific survival outcomes adjusted using propensity score-based weighting. Factors associated with outcomes were assessed via multivariable models using multiple imputation. The median age at diagnosis was 53 years, most patients were male (n = 270), and many had HIV (n = 164). The median OS was 5.0 years, with a median PFS of 1.4 years. Patients living with HIV had the best outcomes, whereas patients with prior organ transplantation had the worst outcomes. Use of higher intensity chemotherapy regimens and use of a proteasome inhibitor in the frontline setting did not show survival benefit. While there was no clear optimal treatment approach in the frontline setting, the median OS of 5.0 years is dramatically improved compared with historical controls.
    DOI:  https://doi.org/10.21203/rs.3.rs-7607922/v1
  36. Radiol Imaging Cancer. 2025 Nov;7(6): e259036
    The SCARLET Trial: Radiotheranostics in Multiple Myeloma.
    Sanchay Jain, Michael M Graham.
      
    DOI:  https://doi.org/10.1148/rycan.259036
  37. bioRxiv. 2025 Oct 02. pii: 2025.09.30.679569. [Epub ahead of print]
    PSP-0119: Targeted IRAK4 Degradation as a Novel Therapeutic Strategy for FLT3-Mutant AML.
    Negar Khazan, Cameron Wa Snyder, Chandhana Ravi, Elizabeth Lamere, Niloy A Singh, Manoj K Khera, Jane Liesveld, Srinivasan Ekambaram, Nikolay V Dokholyan, Myla Strawderman, Kyu Kwang Kim, Rachael Rowswell-Turner, Michael W Becker, Richard G Moore, Rakesh K Singh.
      Acute Myeloid Leukemia (AML) is a life-threatening hematologic malignancy. Despite recent therapeutic advances, rising incidence rates emphasize the urgent need for identification of new targets and therapies. Roles of interleukin receptor-associated kinases IRAK1/4 are emerging in hematologic and solid malignancies. In AML, IRAK4 mRNA is overexpressed at diagnosis, relapses, in residual disease, and in FLT3-ITD-mutant cells, MDS, MPN, and MDS/MPN-negative subtypes. Compared with hematopoietic stem cells, IRAK4 is elevated in t(15;17), inv(16)/t(16;16), and t(11q23)/MLL subtypes, correlating with poor survival. Here, we disclose anti-AML activity of PSP-0119, a novel IRAK4 PROTAC degrader. PSP-0119, inhibited IRAK4 kinase activity, NF-κβ activity, and IL-1β-induced IRAK4 phosphorylation. In-silico docking revealed interactions in CRBN/IRAK4/PSP-0119 ternary complex. PSP-0119 degraded IRAK4 in FLT3-mutant AML cell lines sparing FLT3-wild-type AML cells, FLT3-wild-type patient samples, and normal bone-marrow. Bulk-seq of PSP-0119 treated MOLM-13 cells revealed downregulation of eNOS, a poor AML prognosticator. PSP-0119 suppressed colony formation, cell viability, and MOLM-13 xenograft growth, and synergized with IRAK1 covalent inhibitor JH-X-119-01. PSP-0119 is metabolically stable, retaining 71% of parent compound at 60 minutes in human liver microsomes. In summary, IRAK4 degradation via PSP-0119 as a promising therapeutic strategy for treatment of FLT3-mutant AML.
    DOI:  https://doi.org/10.1101/2025.09.30.679569
  38. Front Oncol. 2025 ;15 1613777
    Efficacy and safety of inotuzumab ozogamicin and its combination therapies in acute lymphoblastic leukemia: a systematic review and meta-analysis.
    Changtao Lao, Jiange Wen, Yuezhen Wen.
       Background: Although treatment for acute lymphoblastic leukemia (ALL) has advanced considerably, adults with relapsed or refractory (R/R) disease continue to face a grave prognosis. Inotuzumab ozogamicin (InO), a CD22-directed antibody-drug conjugate, represents a promising development for B-cell ALL. This systematic review and meta-analysis aims to define the precise efficacy and safety profile of InO-based therapies-both monotherapy and combination regimens-in adults with newly diagnosed and R/R ALL.
    Methods: A systematic literature search was conducted in PubMed, Web of Science, Embase, the Cochrane Library, and clinical trial registries through 2 December 2024. The primary outcomes were overall response (OR), complete remission (CR), minimal residual disease (MRD) negativity, overall survival (OS), and the rate of stem cell transplantation (SCT). Secondary outcomes comprised adverse events (AEs) and relapse.
    Results: The meta-analysis included 1 randomized controlled trial (RCT), 14 single-arm studies, and 1 clinical trial, encompassing 1,068 patients. The pooled efficacy outcomes were as follows: OR rate:89.0% [95% confidence interval (CI): 85.8%-92.2%, 95% prediction interval (PI): 1.2%-99.9%; I 2 = 90.1%, p<0.001], CR rate: 70.5% (95% CI: 58.6%-82.5%, 95% PI: 3.3%-76.9%; I 2 = 94.0%, p<0.001), MRD- rate: 84.6% (95% CI: 79.5%-89.6%, 95% PI: 0.4%-99.8%; I 2 = 80.9%, p<0.001), 1-year OS rate: 61.7% (95% CI: 44.9%-78.5%; I 2 = 94.1%, p<0.001), 2-year OS rate: 51.4% (95% CI: 32.2%-70.7%; I 2 = 93.8%, p<0.001), 3-year OS rate: 46.9% (95% CI: 22.5%-71.4%, 95%; I 2 = 95.2%, p<0.001), 5-year OS rate: 44.9% (95% CI: 39.2%-50.5%, 95%; I 2 = 0.0%, p =0.482), SCT rate: 27.5% (95% CI: 16.6%-38.4%, 95% PI: 1.2%-79.4%; I 2 = 95.2%, p<0.001), relapse rate: 23.6% (95% CI: 16.6%-30.6%, 95% PI: 16.6%-99.6%; I 2 = 78.2%, p<0.001), and incidence of veno-occlusive disease (VOD): 6.2% (95% CI: 3.8%-8.6%, 95% PI: 6.6%-54.5%; I 2 = 68.0%, p<0.001).
    Conclusion: InO demonstrates significant efficacy and a manageable safety profile in adult patients with ALL, supporting its use as a viable therapeutic option. Further randomized studies are needed to validate these findings.
    Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024619042.
    Keywords:  acute lymphoblastic leukemia; efficacy; inotuzumab ozogamicin; meta-analysis; systemic review
    DOI:  https://doi.org/10.3389/fonc.2025.1613777
  39. Br J Haematol. 2025 Nov 17.
    A matching-adjusted indirect comparison of survival outcomes with pirtobrutinib (BRUIN) versus standard of care (SCHOLAR-2) in relapsed/refractory mantle cell lymphoma previously treated with a covalent Bruton tyrosine kinase inhibitor.
    Georg Heß, Toby A Eyre, Min-Hua Jen, Jiewen Zhang, Benjamin Goebel, Sarang Abhyankar, Martin Dreyling.
      
    Keywords:  covalent BTK inhibitor; non‐covalent BTK inhibitor; pirtobrutinib; relapsed/refractory mantle cell lymphoma
    DOI:  https://doi.org/10.1111/bjh.70237
  40. Blood Adv. 2025 Nov 19. pii: bloodadvances.2025018090. [Epub ahead of print]
    Rapid loss of viability in acute myeloid leukemia cells upon telomerase inactivation.
    Elisa A Aquilanti, Lauren Kageler, Vincent Bozinov, Matthew L Meyerson.
      
    DOI:  https://doi.org/10.1182/bloodadvances.2025018090
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